The mechanisms of replication of chromosomal DNA, repair of DNA damage, and their association with cell cycle control are central processes in the maintenance of the integrity of DNA. Our research is focused on two parts of this DNA maintenance machinery, namely (1) on the roles of specific DNA polymerases in chromosomal DNA replication and (2) on protein level response to DNA damage and other replication blocks.
We have found that B subunits of replicative DNA polymerases from archaea to human belong to the same protein family. Since these subunits are essential for viability of cells they are likely to have a common crucial function. We aim to solve this function and the structural basis for it by using recombinant proteins representing multiple distinct species. We have recently also identified several proteins that are involved in cellular response to DNA damage and other replication blocks. These proteins belong to signalling pathways that first identify the problem at the DNA level, stop the replication and, subsequently, signal the cell cycle to stop to provide time for removal of the problem. After the lesion has been removed the replication and cell cycle is resumed. Very severe DNA damage leads to apoptosis. Our interest is focused on interactions of the proteins in these signalling pathways including structural basis of these interactions.